The roles of HOXD10 in the development and progression of head and neck squamous cell carcinoma (HNSCC).
The roles of HOXD10 in the development and progression of head and neck squamous cell carcinoma (HNSCC).
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DOI：
10.1038/bjc.2014.372
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发表时间：
2014-08-12
影响因子：
8.8
通讯作者：
Hunter, K. D.
中科院分区：
文献类型：
--
作者：
Hakami, F.;Darda, L.;Stafford, P.;Woll, P.;Lambert, D. W.;Hunter, K. D.
HOX基因表达在许多癌症中发生改变；先前的微阵列揭示了HOX基因在头颈部鳞状细胞癌（HNSCC）中的表达变化，特别是HOXD10。采用体外qPCR、免疫印迹法和组织免疫组化法检测HOXD10的表达。将低表达细胞稳定转染HOXD10，通过MTS、迁移和粘附试验评估其表型，并与高表达HOXD10细胞中siRNA敲低的影响进行比较。新的HOXD10靶点通过表达微阵列识别，通过报告基因法确认，并通过免疫组化在组织中进行验证。HOXD10在NOKs中表达低，在大多数原发肿瘤细胞中表达高，在淋巴结转移细胞中表达低，组织免疫组化证实了这一模式。过表达HOXD10可减少细胞侵袭，但增加细胞增殖、粘附和迁移，而下调HOXD10可产生相互作用。对细胞凋亡没有一致的影响。微阵列分析鉴定了几种可能的hoxd10应答基因，包括血管运动素（AMOT-p80）和miR-146a。通过报告基因实验证实这些是HOXD10的靶点。操纵AMOT-p80表达导致的表型变化与操纵HOXD10表达相似。HOXD10的表达随疾病的阶段而变化，并产生不同的影响：高表达使癌细胞具有增殖和迁移的优势，而低表达可能通过调节AMOT-p80水平部分地支持侵袭/转移。
HOX gene expression is altered in many cancers; previous microarray revealed changes in HOX gene expression in head and neck squamous cell carcinoma (HNSCC), particularly HOXD10. HOXD10 expression was assessed by qPCR and immunoblotting in vitro and by immunohistochemistry (IHC) in tissues. Low-expressing cells were stably transfected with HOXD10 and the phenotype assessed with MTS, migration and adhesion assays and compared with the effects of siRNA knockdown in high-HOXD10-expressing cells. Novel HOXD10 targets were identified using expression microarrays, confirmed by reporter assay, and validated in tissues using IHC. HOXD10 expression was low in NOKs, high in most primary tumour cells, and low in lymph node metastasis cells, a pattern confirmed using IHC in tissues. Overexpression of HOXD10 decreased cell invasion but increased proliferation, adhesion and migration, with knockdown causing reciprocal effects. There was no consistent effect on apoptosis. Microarray analysis identified several putative HOXD10-responsive genes, including angiomotin (AMOT-p80) and miR-146a. These were confirmed as HOXD10 targets by reporter assay. Manipulation of AMOT-p80 expression resulted in phenotypic changes similar to those on manipulation of HOXD10 expression. HOXD10 expression varies by stage of disease and produces differential effects: high expression giving cancer cells a proliferative and migratory advantage, and low expression may support invasion/metastasis, in part, by modulating AMOT-p80 levels.
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影响因子：
46.9
作者：
Ma L;Reinhardt F;Pan E;Soutschek J;Bhat B;Marcusson EG;Teruya-Feldstein J;Bell GW;Weinberg RA
通讯作者：
Weinberg RA
影响因子：
3.3
作者：
Paramasivam M;Sarkeshik A;Yates JR 3rd;Fernandes MJ;McCollum D
通讯作者：
McCollum D
影响因子：
11.2
作者：
Hunter, Keith D.;Thurlow, Johanna K.;Harrison, Paul R.
通讯作者：
Harrison, Paul R.
DOI：
10.1016/j.bbamcr.2007.11.018
发表时间：
2008-03-01
影响因子：
5.1
作者：
Ernkvist, Mira;Birot, Olivier;Holmgren, Lars
通讯作者：
Holmgren, Lars
影响因子：
11.2
作者：
Hurst DR;Edmonds MD;Scott GK;Benz CC;Vaidya KS;Welch DR
通讯作者：
Welch DR